Perforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination
Autor(a) principal: | |
---|---|
Data de Publicação: | 2009 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/31842 http://dx.doi.org/10.1128/IAI.01459-08 |
Resumo: | A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4(+) and CD8(+) T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4(+) and CD8(+) T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-gamma) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. in spite of a normal numeric expansion, specific CD8(+) T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-gamma or IFN-gamma/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-gamma in the presence of highly cytotoxic T cells. Vaccinated IFN-gamma-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-gamma in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy. |
id |
UFSP_ca69f40216adabe06d12928c4afbc5f3 |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br:11600/31842 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
spelling |
Alencar, Bruna C. G. de [UNIFESP]Persechini, Pedro M.Haolla, Filipe A. [UNIFESP]Oliveira, Gabriel deSilverio, Jaline C.Lannes-Vieira, JoseliMachado, Alexandre V.Gazzinelli, Ricardo T.Bruna-Romero, OscarRodrigues, Mauricio M. [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Universidade Federal do Rio de Janeiro (UFRJ)Fiocruz MSUniversidade Federal de Minas Gerais (UFMG)Univ Massachusetts2016-01-24T13:58:46Z2016-01-24T13:58:46Z2009-10-01Infection and Immunity. Washington: Amer Soc Microbiology, v. 77, n. 10, p. 4383-4395, 2009.0019-9567http://repositorio.unifesp.br/handle/11600/31842http://dx.doi.org/10.1128/IAI.01459-08WOS000269952800022.pdf10.1128/IAI.01459-08WOS:000269952800022A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4(+) and CD8(+) T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4(+) and CD8(+) T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-gamma) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. in spite of a normal numeric expansion, specific CD8(+) T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-gamma or IFN-gamma/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-gamma in the presence of highly cytotoxic T cells. Vaccinated IFN-gamma-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-gamma in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Millennium Institute for Vaccine Development and TechnologyMillennium Institute for Gene TherapyFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Universidade Federal de São Paulo, Escola Paulista Med, CINTERGEN, BR-04044010 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04044010 São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Ctr Ciencias Saude, BR-21941 Rio de Janeiro, BrazilFiocruz MS, Inst Oswaldo Cruz, Lab Biol Celular & Biol Interacoes, BR-21045900 Rio de Janeiro, BrazilUniv Fed Minas Gerais, Dept Bioquim & Imunol, Inst Ciencias Biol, BR-31270901 Belo Horizonte, MG, BrazilFiocruz MS, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG, BrazilUniv Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USAUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, BR-31270901 Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, CINTERGEN, BR-04044010 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, BR-04044010 São Paulo, BrazilFAPESP: 2006/1983-4Millennium Institute for Vaccine Development and Technology: CNPq-420067/2005-1FAPEMIG: EDT 24.000Web of Science4383-4395engAmer Soc MicrobiologyInfection and ImmunityPerforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccinationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000269952800022.pdfapplication/pdf2397960${dspace.ui.url}/bitstream/11600/31842/1/WOS000269952800022.pdfa8998d93d76ba89c253a6374696abbb4MD51open accessTEXTWOS000269952800022.pdf.txtWOS000269952800022.pdf.txtExtracted texttext/plain79852${dspace.ui.url}/bitstream/11600/31842/2/WOS000269952800022.pdf.txtcd81cd6bea3f89be38d2934bd734995dMD52open access11600/318422022-09-27 14:37:29.723open accessoai:repositorio.unifesp.br:11600/31842Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-09-27T17:37:29Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Perforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination |
title |
Perforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination |
spellingShingle |
Perforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination Alencar, Bruna C. G. de [UNIFESP] |
title_short |
Perforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination |
title_full |
Perforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination |
title_fullStr |
Perforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination |
title_full_unstemmed |
Perforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination |
title_sort |
Perforin and Gamma Interferon Expression Are Required for CD4(+) and CD8(+) T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination |
author |
Alencar, Bruna C. G. de [UNIFESP] |
author_facet |
Alencar, Bruna C. G. de [UNIFESP] Persechini, Pedro M. Haolla, Filipe A. [UNIFESP] Oliveira, Gabriel de Silverio, Jaline C. Lannes-Vieira, Joseli Machado, Alexandre V. Gazzinelli, Ricardo T. Bruna-Romero, Oscar Rodrigues, Mauricio M. [UNIFESP] |
author_role |
author |
author2 |
Persechini, Pedro M. Haolla, Filipe A. [UNIFESP] Oliveira, Gabriel de Silverio, Jaline C. Lannes-Vieira, Joseli Machado, Alexandre V. Gazzinelli, Ricardo T. Bruna-Romero, Oscar Rodrigues, Mauricio M. [UNIFESP] |
author2_role |
author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Universidade Federal do Rio de Janeiro (UFRJ) Fiocruz MS Universidade Federal de Minas Gerais (UFMG) Univ Massachusetts |
dc.contributor.author.fl_str_mv |
Alencar, Bruna C. G. de [UNIFESP] Persechini, Pedro M. Haolla, Filipe A. [UNIFESP] Oliveira, Gabriel de Silverio, Jaline C. Lannes-Vieira, Joseli Machado, Alexandre V. Gazzinelli, Ricardo T. Bruna-Romero, Oscar Rodrigues, Mauricio M. [UNIFESP] |
description |
A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4(+) and CD8(+) T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4(+) and CD8(+) T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-gamma) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. in spite of a normal numeric expansion, specific CD8(+) T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-gamma or IFN-gamma/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-gamma in the presence of highly cytotoxic T cells. Vaccinated IFN-gamma-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-gamma in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy. |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-10-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:58:46Z |
dc.date.available.fl_str_mv |
2016-01-24T13:58:46Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Infection and Immunity. Washington: Amer Soc Microbiology, v. 77, n. 10, p. 4383-4395, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/31842 http://dx.doi.org/10.1128/IAI.01459-08 |
dc.identifier.issn.none.fl_str_mv |
0019-9567 |
dc.identifier.file.none.fl_str_mv |
WOS000269952800022.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1128/IAI.01459-08 |
dc.identifier.wos.none.fl_str_mv |
WOS:000269952800022 |
identifier_str_mv |
Infection and Immunity. Washington: Amer Soc Microbiology, v. 77, n. 10, p. 4383-4395, 2009. 0019-9567 WOS000269952800022.pdf 10.1128/IAI.01459-08 WOS:000269952800022 |
url |
http://repositorio.unifesp.br/handle/11600/31842 http://dx.doi.org/10.1128/IAI.01459-08 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Infection and Immunity |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
4383-4395 |
dc.publisher.none.fl_str_mv |
Amer Soc Microbiology |
publisher.none.fl_str_mv |
Amer Soc Microbiology |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
bitstream.url.fl_str_mv |
${dspace.ui.url}/bitstream/11600/31842/1/WOS000269952800022.pdf ${dspace.ui.url}/bitstream/11600/31842/2/WOS000269952800022.pdf.txt |
bitstream.checksum.fl_str_mv |
a8998d93d76ba89c253a6374696abbb4 cd81cd6bea3f89be38d2934bd734995d |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764176262692864 |